Oseltamivir Prescribing in Pharmacy-Benefits Database, United States, 2004–2005

We reviewed information from a US pharmacy benefits manager database from 2004 through 2005 during periods with little influenza activity. We calculated rates of oseltamivir prescriptions to enrollees. Prescription rates increased significantly from 27.3/100,000 in 2004 to 134/100,000 in 2005 (p<0.05), which suggested that personal stockpiling of oseltamivir occurred.


F rom 2003 through 2006, avian infl uenza virus (H5N1)
spread from Southeast Asia to Africa, Europe, and the Middle East (1), and media coverage about the risk for human infection and the potential for an infl uenza pandemic increased. Two classes of medications are available to treat infl uenza: neuraminidase inhibitors (NIs), which include oseltamivir and zanamivir, and adamantanes, which include amantadine and rimantadine (2). NIs are recommended by the World Health Organization for treatment of avian infl uenza virus (H5N1) infection because isolates have shown adamantane resistance (3). During the fall of 2005, NIs were in limited supply (4).
In 2005, concern was expressed in the medical literature about possible personal stockpiling of NIs for use during an infl uenza pandemic (5). We undertook this study to look for evidence of oseltamivir stockpiling, to understand the magnitude of the practice, and to discern who was receiving and prescribing these drugs. We collaborated with a pharmacy benefi ts management company to examine antiviral prescriptions and oseltamivir prescription fi lling in the United States during calendar weeks 36-44 in 2004 and 2005. These weeks were chosen because they had little infl uenza activity in either year and because reports of oseltamivir stockpiling occurred during this period in 2005 (6-9).

The Study
We used a database from Medco Health Solutions, Inc. (Franklin Lakes, NJ, USA), a pharmacy benefi ts manage-ment company serving >50 million US members. We examined fi lled prescriptions for oseltamivir by members from January 2002 through May 2006. Available member data included demographic information, medication dispensed, prescriber identifi cation, and pharmacy dispensing history. Member-level historic pharmacy dispensing data were used to assign members into chronic disease classifi cations (10). Prescribers were cross-referenced with an American Medical Association member database to determine specialty and years since medical school graduation. We were able to cross-reference 64% of prescribing physicians by specialty and years since medical school graduation. The Centers for Disease Control and Prevention (Atlanta, GA, USA) determined that institutional review board approval was not needed for this study because we received aggregated data that was anonymous and not identifi ed.
To assess media coverage, we queried the LexisNexis US News database (www.lexisnexis.com) for total weekly news reports from August 1, 2003, through August 30, 2006, referring to avian infl uenza and oseltamivir. Weekly virologic data from the World Health Organization and National Respiratory and Enteric Virus Surveillance System collaborating laboratories were used to assess US infl uenza activity during 2004 and 2005 (6,7).
Oseltamivir prescription rates were calculated per 100,000 enrolled members and per 1,000 prescribing physicians. Binomial distributions were used to estimate variances for rates. Relative rate ratios (RRs) and 95% confidence intervals (CIs) were calculated for 2004 and 2005 data. P values <0.05 were considered statistically significant. Analyses were performed with SAS version 9.0 statistical software (SAS Institute, Cary, NC, USA).
Weekly rates of fi lled prescriptions for oseltamivir and percentage of samples positive for infl uenza from October 1, 2002, through June 1, 2006, were temporally associated before the 2005-06 infl uenza season ( Figure 1). During the fall of 2005, prescriptions for oseltamivir increased without an associated increase in the percentage of samples testing positive for infl uenza. In contrast, during the same period there was a temporal relationship between weekly oseltamivir prescription rates and media reports of avian infl uenza and oseltamivir ( Figure 1).
The proportion of oseltamivir prescriptions to total anti-infl uenza prescriptions increased from 37.0% in 2004 to 76.9% in 2005 ( Among adults, prescription rates were consistently higher in 2005 than in 2004, irrespective of chronic disease classifi cation (Table 2). In 2005, the highest oseltamivir prescription rate was 268.5/100,000 for enrollees with pulmonary disease, and the lowest rate was 89.5/100,000 for those without chronic disease. The greatest rate increase from 2004 to 2005 occurred among those without chronic disease (RR 6.36, 95% CI 6.10-6.62). Among enrollees of all ages during weeks 36-44 in 2005, approximately one third of oseltamivir prescriptions were fi lled by members without chronic disease.
For all prescribers in 2004 and 2005, oseltamivir prescription rates increased with years since the prescriber's medical school graduation. The lowest prescription rate in 2005 (1.7/1,000) was observed in prescribers who graduated from medical school in the previous 5 years, followed by prescribers with 5-10 years (4.9/1,000) and 11-19 years (6.6/1,000) since graduation. The highest rate (10.4/1,000) was observed in prescribers with >20 years since graduation.

Conclusions
Rates of fi lled oseltamivir prescriptions during calendar weeks 36-44 increased from 2004 to 2005. These weeks in 2005 were noteworthy for increased media references to oseltamivir and avian infl uenza, although there was little infl uenza activity. Low levels of infl uenza-like illness and respiratory syncytial virus activity also were documented during this period (6,11).
Among Medco enrollees, the highest prescription rates were for groups with the greatest risk for infl uenza-associated complications: persons >50 years of age and adults with chronic diseases (2). However, oseltamivir prescrip-  Physician prescribing rates for all specialties increased from 2004 toh 2005. Prescription rates in 2004 were highest for general internists and family practitioners and likely refl ect the primary care physician's gatekeeper role as the entry point for those seeking medical care. Given the nature of their specialty, infectious diseases physicians may be asked to prescribe oseltamivir for personal stockpiles more than the typical provider. Because physicians need not honor all prescription requests, these increases may not be fully explained by increased patient requests because physician attitudes regarding personal stockpiling likely affected whether requests were made or honored.
Our study is subject to limitations. Although we studied a large, national population, our study population may not be nationally representative. In addition, our analyses were limited to prescriptions of oseltamivir that were fi lled by a pharmacy, and we do not know whether prescriptions were written with the expressed purpose of personal stockpiling for use during a pandemic.
In summary, our fi ndings suggest that increased media reports during the fall of 2005 about the infl uenza (H5N1) epizootic prompted concern about the possibility of an infl uenza pandemic. This heightened concern led to an increase in fi lled oseltamivir prescriptions for personal stockpiling among a national pharmacy benefi ts member population. Subsequently, as infl uenza virus began circulating in early 2006, oseltamivir prescriptions corresponded more closely with virus activity. Efforts by federal and state governments to procure suffi cient supplies of NIs to treat every patient likely to become ill during the next pandemic may quell demand in personal stockpiles. Education campaigns about appropriate use of antiviral medications that target physicians and patients during seasonal epidemics and pandemics may reduce inappropriate requests for oseltamivir and other drugs. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 8, August 2008 primary research interest is the clinical epidemiology of respiratory infections.